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1.
Zhongguo Gu Shang ; 34(11): 1034-9, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34812021

RESUMO

OBJECTIVE: To explore the clinical application of Orthopedic Tianji Robot in the treatment of thoracolumbar fractures with minimally invasive percutaneous pedicle screw internal fixation. METHODS: The clinical data of 46 patients with thoracolumbar fractures treated by minimally invasive percutaneous pedicle screw internal fixation from June 2018 to January 2020 in Gansu Provincial People's Hospital was retrospectively analyzed. According to the different aided equipments, the patients were divided into a C-arm X-ray plus robot assisted nail placement group (observation group) and simple C-arm X-ray assisted nail placement group (control group). Twenty-two patients in observation group, including 12males and 10 females, aged from 24 to 61 years old, with a mean of(40.23±12.19) years, 3 cases were T11 vertebrae fracture, 8 cases were T12, 9 cases were L1, and 2 cases were L2. And there were 24 cases in control group, including 15 males and 9 females, aged from 26 to 58 years old, with a mean of (42.88±10.31) years, 3 cases were T11 vertebrae fracture, 10 cases were T12, 7 cases were L1, and 4 cases were L2. The operation time, the number of intraoperative fluoroscopy, intraoperative blood loss, the days of hospitalization, and postoperative complications were recorded. Preoperative and postoperative VAS at 3 days, 1 week and 3 months were compared between two groups. The sagittal Cobb angle of the injured vertebral body and the percentage of the anterior edge height of the vertebral body were observed before and after operation, and evaluate the accuracy of nail placement according to the Gertzbein-Robbins classification criteria with collected postoperative CT images. RESULTS: All patients were followed up for 5 to 12 months with an average of (7.07±0.83) months. There was no significant differences in intraoperative blood loss, operation time and hospitalization days between two groups (P>0.05). The number of intraoperative fluoroscopy was (5.62±0.51) times in observation group and (12.54±0.52) in control group, the difference between two groups was statistically significant (P<0.05). The VAS, the percentage of the height of the injured vertebra anterior edge and the Cobb angle of the injured vertebral plane at each time point after operation were improved(P<0.05), but the difference between two groups was not statistically significant (P>0.05). One case of postoperative incision infection occurred in the control group, which was cured after active dressing changes. There were no serious complications such as screw loosening and breakage in all patients, and there was no statistically significant difference in the incidence of complications between two groups(P>0.05). The postoperative nail placement accuracy ratesof the observation group and the control group were 98.4% (126/128) and 90.3% (121/134), respectively, and the difference was statistically significant (P<0.05). CONCLUSION: In the surgical treatment of thoracolumbar fractures, compared with simple C-arm fluoroscopy, the pedicle screw placement assisted by Orthopedic Tianji Robot overcomes the shortcomings of surgeon's physiological tremor, fatigue and multiple intraoperative fluoroscopy, improves the accuracy of screw placement, and is a more accurate and safer way of pedicle screw placement for thoracolumbar fractures.


Assuntos
Parafusos Pediculares , Robótica , Adulto , Feminino , Fixação Interna de Fraturas , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
2.
J Cancer ; 12(12): 3715-3725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995646

RESUMO

Background: Decision-making regarding biochemical recurrence (BCR) in localized prostate cancer (PCa) patients after radical prostatectomy (RP) mainly relies on clinicopathological parameters with a low predictive accuracy. Currently, accumulating evidence suggests that immune-associated genes (IAGs) play irreplaceable roles in tumorigenesis, progression and metastasis. Considering the critical role of immune in PCa, we therefore attempted to identify the novel IAGs signature and validate its prognostic value that can better forecast the risk for BCR and guide clinical treatment. Methods: RNA-sequencing and corresponding clinicopathological data were downloaded from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA) was utilized to screen out the candidate module closely related to BCR, and univariate and LASSO Cox regression analyses were performed to build the gene signature. Kaplan-Meier (KM) survival analysis, time-dependent receiver operating curve (ROC), independent prognostic analysis and nomogram were also applied to evaluate the prognostic value of the signature. Besides, Gene ontology analysis (GO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to explore potential biological pathways. Results: A total of six IAGs (SSTR1, NFATC3, NRP1, TUBB3, IL1R1, GDF15) were eventually identified and used to establish a novel IAGs signature. The Kaplan-Meier analysis revealed that patients with low-risk scores had longer recurrence-free survival (RFS) than those with high-risk scores in both GSE70769 and TCGA cohorts. Further, our signature was also proven to be a valuable independent prognostic factor for BCR. We also constructed a nomogram based on the gene signature and related clinicopathologic features, which excellently predict 1-year, 3-year and 5-year prognosis of localized PCa patients after RP. Moreover, functional enrichment analysis demonstrated the vital biological processes, and stratified GSEA revealed that a crucial immune-related pathway (T cell receptor signaling pathway) was notably enriched in the high-risk group. Conclusions: We successfully developed a novel robust IAGs signature that is powerful in BCR prediction in localized PCa patients after RP, and created a prognostic nomogram. In addition, the signature might help clinicians in selecting high-risk subpopulation, predicting survival status of patients and promoting more individualized therapies than traditional clinical factors.

3.
Expert Rev Vaccines ; 20(7): 891-898, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33929930

RESUMO

Background: Although the inactivated SARS-CoV-2 vaccine (CoronaVac) has undergone preclinical tests and clinical trials evaluating its efficacy and safety, few data have been reported in the post-licensure real-world setting. We aimed to assess the safety of the vaccine among healthcare workers.Methods: A self-administered online survey on monitoring adverse reactions post vaccination was conducted among the staff who worked at and were vaccinated in a tertiary hospital in Taizhou, China, from February 24 to 7 March 2021. A total of 1526 subjects responded to the questionnaire when they received an e-mail or an e-poster on WeChat.Results: The incidences of overall adverse reactions after the first and second injections were 15.6% (238/1526) and 14.6% (204/1397), respectively. The most common adverse reaction was localized pain at the injection site, with an incidence of 9.6% and 10.7% after each dose, accounting for 61.8% and 73.0% of adverse reactions, respectively. Fatigue, muscle pain, and headache were the most common systemic adverse reactions.Conclusions: These findings implied that the inactivated CoronaVac vaccine has an acceptable safety profile among healthcare workers due to the low incidence of self-reported adverse reactions. This may boost public confidence in nationwide mass vaccination campaigns.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Pessoal de Saúde , Autorrelato , Vacinas de Produtos Inativados/administração & dosagem , Adolescente , Adulto , COVID-19/epidemiologia , Vacinas contra COVID-19/efeitos adversos , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas de Produtos Inativados/efeitos adversos , Adulto Jovem
4.
Biomark Med ; 14(12): 1127-1137, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32969244

RESUMO

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan-Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

5.
Oncol Lett ; 18(2): 1863-1871, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423255

RESUMO

Contactin 3 (CNTN3) is a member of the contactin family that is primarily expressed in the nervous system. However, to the best of our knowledge, expression of contactin and its role in the development and progression of brain tumours has not been studied. Although glioblastoma multiforme (GBM) is the most common malignant brain tumour, advances in therapeutic options for patients with GBM have been modest due to an incomplete understanding of the molecular mechanisms underlying development and progression. The aim of the present study was to examine the correlation between CNTN3 and its associated genes and the clinical outcome in patients with GBM. CNTN3 and the expression levels of associated genes were analysed in GBM datasets obtained from the SAGE Anatomical viewer website, Gene Expression Omnibus, Oncomine and The Cancer Genome Atlas. CNTN3 was significantly downregulated in patients with GBM. Subsequently, the expression of CNTN3 was further validated using immunohistochemistry in a cohort of GBM specimens. The immunohistochemistry results were consistent with the in silico analyses. Kaplan-Meier analysis indicated that patients with lower expression levels of CNTN3 had a significantly shorter overall survival (OS) time compared with patients with higher levels of CNTN3 expression. Univariate and multivariate Cox regression analyses demonstrated that CNTN3 expression was an independent prognostic indicator in patients with GBM. Furthermore, gene set enrichment analysis revealed that CNTN3 was associated with the receptor tyrosine-protein kinase (ErbB) signalling pathway. In the ErbB signalling pathway, epidermal growth factor receptor (EGFR) was negatively correlated with CNTN3. Taken together, these data suggest that lower expression levels of CNTN3 may be an independent biomarker that predicts poor OS time in patients with GBM, and that EGFR expression in the ErbB pathway may be associated with CNTN3 expression.

6.
J Orthop Surg Res ; 14(1): 276, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455401

RESUMO

BACKGROUND: There were several reports describing the biomechanics and microstructure of multifidus muscles in patients with lumbar disc herniation. However, correlations between lumbar multifidus muscle atrophy (LMA), spinopelvic parameters, and severity of adult degenerative scoliosis (ADS) have not been investigated. The study evaluated the impact of LMA and spinopelvic parameters on the severity of ADS. METHODS: One hundred and thirty-two patients with ADS were retrospectively reviewed. Standing whole-spine X-ray was used to evaluate the coronal (coronal Cobb angle, CA; coronal vertical axis, CVA) and sagittal (sagittal vertical axis, SVA; thoracic kyphosis, TK; lumbar lordosis, LL; pelvic incidence, PI; pelvic tilt, PT; sacral slope, SS) parameters. LMA was evaluated on axial T2-weighted magnetic resonance imaging (MRI) at intervertebral levels above and below the vertebra at the apex of the scoliotic curve. Clinical symptoms were evaluated by the Oswestry Disability Index (ODI) and the Japanese Orthopaedic Association (JOA) score. Multiple linear regression was used to assess correlations between LMA, spinopelvic parameters, and severity of scoliosis. RESULTS: LL and PT were negatively correlated with CA (P < 0.001); LL was positively correlated with SVA (P < 0.001). PI was positively correlated with CA (P < 0.001) and CVA (P < 0.001). PT (P < 0.001) and SS (P < 0.001) were negatively correlated with CVA. SS was negatively correlated with SVA (P < 0.001). Concave LMA at the upper or lower intervertebral level of the apical vertebra was positively correlated with CA (P ≤ 0.001); convex LMA at the upper or lower intervertebral level was negatively correlated with CA (P < 0.001). Convex LMA at the upper intervertebral level and concave LMA at the lower intervertebral level of the apical vertebra were negatively correlated with the SVA (P ≤ 0.001). At the upper intervertebral level, LMA on the concave side was positively correlated with CVA (P = 0.028); LMA on the convex side was negatively correlated with CVA (P = 0.012). PI was positively correlated with ODI (P < 0.001); PT (P < 0.001) and SS (P < 0.001) were negatively correlated with ODI. At the lower intervertebral level, LMA on the concave side was positively correlated with ODI (P = 0.038); LMA on the convex side was negatively correlated with ODI (P = 0.011). PI was positively correlated with JOA (P < 0.001); PT (P < 0.001) and SS (P < 0.001) were negatively correlated with JOA. CONCLUSIONS: Spinopelvic parameters are correlated with the severity of ADS. Asymmetric LMA at both upper and lower intervertebral levels of the apical vertebra is positively correlated with CA. LMA on the diagonal through the apical vertebra is very important to maintain sagittal imbalance via parallelogram effect. LMA at lower intervertebral levels of the apical vertebra may have a predictive effect on ODI. JOA score seems to be more correlated with spinopelvic parameters than LMA.


Assuntos
Vértebras Lombares/diagnóstico por imagem , Atrofia Muscular/diagnóstico por imagem , Músculos Paraespinais/diagnóstico por imagem , Ossos Pélvicos/diagnóstico por imagem , Escoliose/diagnóstico por imagem , Índice de Gravidade de Doença , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Muscular/epidemiologia , Estudos Retrospectivos , Escoliose/epidemiologia
7.
Medicine (Baltimore) ; 98(25): e16185, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232977

RESUMO

BACKGROUND: Most of the previous studies combined all types of intramedullary ependymomas without providing accurate pathological subtypes. In addition, it was very difficult to evaluate the factors associated with postoperative outcomes of patients with different pathological subtypes of intramedullary Grade II ependymomas by traditional meta-analysis. This study evaluated the factors related with postoperative outcomes of patients with intramedullary Grade II ependymomas. METHODS: Individual patient data analysis was performed using PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The search included articles published up to April 2018 with no lower date limit on the search results. The topics were intramedullary Grade II ependymomas. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier survival analysis (log-rank test). The level of significance was set at P < .05. RESULTS: A total of 21 studies with 70 patients were included in this article. PFS of patients who underwent total resection was much longer than the PFS of those who received subtotal resection (P < .001). Patients who received adjuvant therapy (P = .005) or radiotherapy and chemotherapy (P < .001) seemed to have shorter PFS than others; PFS of patients who had cerebrospinal fluid disease dissemination (P = .022) or scoliosis (P = .001) were significantly shorter than others. OS of cellular ependymoma patients was less than giant cell ependymoma patients (P < .001). CONCLUSIONS: PFS of patients who received total resection was much longer than those who received subtotal resection. Patients treated with adjuvant therapy or radiotherapy and chemotherapy appeared to have shorter PFS than others; PFS of patients with cerebrospinal fluid disease dissemination or scoliosis were significantly shorter than others. Cellular ependymomas would have better OS than giant cell ependymoma. However, giant cell ependymoma patients might have the worst OS.


Assuntos
Ependimoma/cirurgia , Complicações Pós-Operatórias/classificação , Resultado do Tratamento , Adulto , Ependimoma/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Neoplasias da Medula Espinal/cirurgia , Análise de Sobrevida
8.
Ann Hematol ; 98(4): 987-996, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30715567

RESUMO

Epstein-Barr virus (EBV) reactivation is a life-threatening complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT). In this study, we investigated the characteristics of EBV reactivation in 186 consecutive myelodysplastic (MDS) patients who underwent allo-HSCT in our centre. In 35 patients (18.8%) who experienced EBV reactivation after allo-HSCT, the median onset was 53 days (range 4-381 days). The cumulative incidence of EBV reactivation at the first, sixth, and twelfth month after allo-HSCT was 10.7%, 15.1%, and 17.9%, respectively. Twenty-five patients (71.4%) received pre-emptive rituximab therapy, and no patients developed post-transplant lymphoproliferative disorders. Stem cell source was proven to be a risk factor correlated with EBV reactivation. The cumulative incidence of relapse in the EBV-positive group was 11.4%, 25.2%, and 31.0% at the first, second, and third year after transplantation, respectively, being significantly higher than the corresponding 6.8%, 10.2%, and 10.2%, in the EBV-negative group (P = 0.014). Prognostic analysis showed that EBV reactivation was an independent risk factor for relapse-free survival (RFS). Patients in the EBV-positive group showed obviously shorter RFS than those in the EBV-negative group, with 3-year RFS of 62% and 85%, respectively (P = 0.017).


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4 , Síndromes Mielodisplásicas , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Fatores de Risco , Rituximab/administração & dosagem , Taxa de Sobrevida , Fatores de Tempo
9.
Cell Physiol Biochem ; 50(5): 1964-1987, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30396166

RESUMO

BACKGROUND/AIMS: The purpose of this study was to probe the clinico-pathological significance and the underlying mechanism of miR-30d-5p expression in non-small cell lung cancer (NSCLC). METHODS: We initially examined the level of miR-30d-5p expression in NSCLC and non-cancer tissues using RT-qPCR. Then, a series of validation analyses including a meta-analysis of data from microarray chips in Gene Expression Omnibus (GEO), data mining of the cancer genome atlas (TCGA) and an integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies were performed to examine the clinico-pathological value of miR-30d-5p expression in NSCLC. In vitro experiments were further conducted to investigate the impact of miR-30d-5p on NSCLC cell growth. The molecular mechanism by which miR-30d-5p regulates the pathogenesis of NSCLC was probed through a bioinformatics analysis of its target genes. Moreover, dual luciferase reporter assay was conducted to verify the targeting regulatory relationship between miR-30d-5p and CCNE2. RESULTS: Based on results from RT-qPCR, GEO meta-analysis, TCGA data mining and the integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies, miR-30d-5p expression was decreased in NSCLC tissues, and patients with NSCLC who presented with lower miR-30d-5p expression tended to display an advanced clinical progression. Significant pathways including the Mucin type O-glycan biosynthesis pathway, cell cycle pathway and cysteine and methionine metabolism pathway (all P< 0.05) revealed potential roles of the target genes of miR-30d-5p in the oncogenesis of NSCLC. Results from in vitro experiments indicated that miR-30d-5p could attenuate proliferation and viability of NSCLC cells. Among the 12 identified hub genes, nine genes including E2F3, CCNE2, SKP2, CDK6, TFDP1, LDHA, GOT2, DNMT3B and ST6GALNAC1 were validated by Pearson's correlation test and the human protein atlas (HPA) database as targets of miR-30d-5p with higher probability. Specifically, dual luciferase reporter assay confirmed that CCNE2 was directly targeted by miR-30d-5p. CONCLUSION: In summary, miR-30d-5p expression is decreased in NSCLC, and it might play the role as tumor suppressor in NSCLC by regulating target genes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Área Sob a Curva , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Ciclinas/química , Ciclinas/genética , Ciclinas/metabolismo , Bases de Dados Factuais , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Metanálise como Assunto , MicroRNAs/química , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Curva ROC
10.
World J Surg Oncol ; 16(1): 109, 2018 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-29914539

RESUMO

BACKGROUND: This study was carried out to discover the underlying role that HOXA11 plays in lung squamous cancer (LUSC) and uncover the potential corresponding molecular mechanisms and functions of HOXA11-related genes. METHODS: Twenty-three clinical paired LUSC and non-LUSC samples were utilized to examine the level of HOXA11 using quantitative real-time polymerase chain reaction (qRT-PCR). The clinical significance of HOXA11 was systematically analyzed based on 475 LUSC and 18 non-cancerous adjacent tissues from The Cancer Genome Atlas (TCGA) database. A total of 102 LUSC tissues and 121 non-cancerous tissues were available from Oncomine to explore the expressing profiles of HOXA11 in LUSC. A meta-analysis was carried out to further assess the differential expression of HOXA11 in LUSC, including in-house qRT-PCR data, expressing data extracted from TCGA and Oncomine databases. Moreover, the enrichment analysis and potential pathway annotations of HOXA11 in LUSC were accomplished via Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of hub genes and according correlations with HOXA11 were assessed to further explore the biological role of HOXA11 in LUSC. RESULTS: HOXA11 expression in LUSC had a tendency to be upregulated in comparison to adjacent non-cancerous tissues by qRT-PCR. TCGA data displayed that HOXA11 was remarkably over-expressed in LUSC compared with that in non-LUSC samples, and the area under curves (AUC) was 0.955 (P < 0.001). A total of 1523 co-expressed genes were sifted for further analysis. The most significant term enriched in the KEGG pathway was focal adhesion. Among the six hub genes of HOXA11, including PARVA, ILK, COL4A1, COL4A2, ITGB1, and ITGA5, five (with the exception of COL4A1) were significantly decreased compared with the normal lung tissues. Moreover, the expression of ILK was negatively related to HOXA11 (r = - 0.141, P = 0.002). CONCLUSION: High HOXA11 expression may lead to carcinogenesis and the development of LUSC. Furthermore, co-expressed genes might affect the prognosis of LUSC.


Assuntos
Carcinoma de Células Escamosas/genética , Proteínas de Homeodomínio/genética , Neoplasias Pulmonares/genética , Carcinoma de Células Escamosas/sangue , Biologia Computacional , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/sangue , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
11.
Oncol Rep ; 40(1): 226-240, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29749550

RESUMO

The long non­coding RNA (lncRNA) PVT1 plays vital roles in the tumorigenesis and development of various types of cancer. However, the potential expression profiling, functions and pathways of PVT1 in HCC remain unknown. PVT1 was knocked down in SMMC­7721 cells, and a miRNA microarray analysis was performed to detect the differentially expressed miRNAs. Twelve target prediction algorithms were used to predict the underlying targets of these differentially expressed miRNAs. Bioinformatics analysis was performed to explore the underlying functions, pathways and networks of the targeted genes. Furthermore, the relationship between PVT1 and the clinical parameters in HCC was confirmed based on the original data in the TCGA database. Among the differentially expressed miRNAs, the top two upregulated and downregulated miRNAs were selected for further analysis based on the false discovery rate (FDR), fold­change (FC) and P­values. Based on the TCGA database, PVT1 was obviously highly expressed in HCC, and a statistically higher PVT1 expression was found for sex (male), ethnicity (Asian) and pathological grade (G3+G4) compared to the control groups (P<0.05). Furthermore, Gene Ontology (GO) analysis revealed that the target genes were involved in complex cellular pathways, such as the macromolecule biosynthetic process, compound metabolic process, and transcription. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the MAPK and Wnt signaling pathways may be correlated with the regulation of the four candidate miRNAs. The results therefore provide significant information on the differentially expressed miRNAs associated with PVT1 in HCC, and we hypothesized that PVT1 may play vital roles in HCC by regulating different miRNAs or target gene expression (particularly MAPK8) via the MAPK or Wnt signaling pathways. Thus, further investigation of the molecular mechanism of PVT1 in HCC is needed.


Assuntos
Carcinoma Hepatocelular/genética , Biologia Computacional , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Idoso , Carcinogênese , Carcinoma Hepatocelular/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Humanos , Neoplasias Hepáticas/patologia , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Estudos Prospectivos
12.
Int J Oncol ; 53(1): 73-86, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29658571

RESUMO

Homeobox A1 (HOXA1) serves an oncogenic role in multiple cancer types. However, the role of HOXA1 in non­small cell lung cancer (NSCLC) remains unclear. In the present study, use of reverse transcription-quantitative polymerase chain reaction and the databases of The Cancer Genome Atlas (TCGA), Oncomine, Gene Expression Profiling Interactive Analysis and the Multi Experiment Matrix were combined to assess the expression of HOXA1 and its co-expressed genes in NSCLC. Bioinformatic analyses, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and network and protein-protein interaction analyses, were used to investigate the underlying molecular mechanism effected by the co-expressed genes. Additionally, the potential miRNAs targeting HOXA1 were investigated. The results showed that HOXA1 was upregulated in NSCLC. The area under the curve of HOXA1 indicated a moderate diagnostic value of the HOXA1 level in NSCLC. According to GO and KEGG analyses, the co-expressed genes may be involved in 'dGTP metabolic processes', 'network-forming collagen trimers', 'centromeric DNA binding' and 'the p53 signaling pathway'. Three miRNAs (miR­181b­5p, miR­28­5p and miR­181d­5p) targeting HOXA1 were each predicted by 10 algorithms; miR­181b and miR­181d levels were downregulated in LUSC tissues compared with those in normal lung tissues based on data from the TCGA database, and inverse correlations were found between HOXA1 and miR­181b (r=-0.205, P<0.001) and miR­181d (r=-0.106, P=0.020). We speculate that HOXA1 may be the direct target of miR­181b­5p or miR­181d­5p in LUSC, and HOXA1 may serve a significant role in NSCLC by regulating various pathways, particularly the p53 signaling pathway. However, the detailed mechanism should be verified by functional experiments.


Assuntos
Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Homeodomínio/genética , MicroRNAs/genética , Fatores de Transcrição/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Biologia Computacional , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Humanos , Transdução de Sinais , Proteína Supressora de Tumor p53/genética
13.
Int J Food Sci Nutr ; 69(4): 472-479, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28903608

RESUMO

Steviol glycosides, a natural sweetener, may perform bioactivities via steviol, their main metabolite in human digestion. The metabolising kinetics, i.e. glucuronidation kinetics and interaction between steviol glycosides or their metabolites and metabolising enzyme, are important for understanding the bioactivity and cytotoxicity. The present study investigated kinetics of steviol glucuronidation in human liver microsome and a recombinant human UDP-glucuronosyltransferases isomer, UGT2B7, along with molecular docking to analyse interaction between UGT2B7 and steviol or glucose. The active pocket of UGT2B7 is consisted of Arg352, Leu347, Lys343, Phe339, Tyr354, Lys355 and Leu353. The influence of stevioside, rebaudioside A, glucose and some chemotherapy reagents on the glucuronidation was also studied. The predicted hepatic clearence suggested that steviol could be classified as high-clearence drug. The steviol glycosides did not affect the glucuronidation of steviol notably.


Assuntos
Diterpenos do Tipo Caurano/metabolismo , Glucose/metabolismo , Glucosídeos/metabolismo , Glucuronosiltransferase/metabolismo , Microssomos Hepáticos/metabolismo , Humanos , Cinética , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Proteínas Recombinantes
14.
Clin Epigenetics ; 9: 91, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28861128

RESUMO

BACKGROUND: Aberrant CpG island methylation has been increasingly recognized as a common event in myelodysplastic syndrome (MDS). To date, most of the previous studies of miR-124 in MDS have focused on epigenetic changes and little is known about the underlying mechanism through which miR-124 regulates CDK6 expression. RESULTS: In the present study, we employed pyrosequencing analysis to quantify the methylation levels of upstream regions of the miR-124 genes (miR-124-1, miR-124-2 and miR-124-3) in 56 primary MDS patients. We found the three miR-124 genes were methylated in MDS patients. Univariate analysis revealed that the World Health Organization (WHO) classification, marrow blast count, karyotype, International Prognostic Scoring System (IPSS), mean corpuscular volume, as well as high methylation of miR-124-1, miR-124-2 and miR-124-3 were significantly related to overall survival. In leukaemia-free survival, patients who were older and had an advanced WHO classification, high marrow blast counts, high IPSS risk and high methylation of miR-124-1 and miR-124-2 progressed rapidly to acute myeloid leukaemia. Multivariate analysis demonstrated that high methylation of miR-124-3 was an independent factor of overall survival. Median survival of patients with high miR-124-3 methylation was significantly shorter (7.6 months) than patients with low methylation (32.7 months; P = 0.010). A functional study revealed that silencing of miR-124 resulted in upregulation of its target gene, cyclin dependent kinase CDK6, which in turn promoted cell proliferation in the MDS cell line SKM-1. CONCLUSIONS: High methylation of miR-124-3 predicts shorter survival for patients with MDS, which may be a useful prognostic marker in MDS.


Assuntos
Metilação de DNA , MicroRNAs/genética , Síndromes Mielodisplásicas/genética , Análise de Sequência de DNA/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Ilhas de CpG , Quinase 6 Dependente de Ciclina/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Análise de Sobrevida , Adulto Jovem
15.
Cell Death Dis ; 8(7): e2912, 2017 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-28682313

RESUMO

Our previous findings suggest that sphingosine kinase 2 (SPK2) mediates ischemic tolerance and autophagy in cerebral preconditioning. The aim of this study was to determine by which mechanism SPK2 activates autophagy in neural cells. In both primary murine cortical neurons and HT22 hippocampal neuronal cells, overexpression of SPK2 increased LC3II and enhanced the autophagy flux. SPK2 overexpression protected cortical neurons against oxygen glucose deprivation (OGD) injury, as evidenced by improvement of neuronal morphology, increased cell viability and reduced lactate dehydrogenase release. The inhibition of autophagy effectively suppressed the neuroprotective effect of SPK2. SPK2 overexpression reduced the co-immunoprecipitation of Beclin-1 and Bcl-2, while Beclin-1 knockdown inhibited SPK2-induced autophagy. Both co-immunoprecipitation and GST pull-down analysis suggest that SPK2 directly interacts with Bcl-2. SPK2 might interact to Bcl-2 in the cytoplasm. Notably, an SPK2 mutant with L219A substitution in its putative BH3 domain was not able to activate autophagy. A Tat peptide fused to an 18-amino acid peptide encompassing the native, but not the L219A mutated BH3 domain of SPK2 activated autophagy in neural cells. The Tat-SPK2 peptide also protected neurons against OGD injury through autophagy activation. These results suggest that SPK2 interacts with Bcl-2 via its BH3 domain, thereby dissociating it from Beclin-1 and activating autophagy. The observation that Tat-SPK2 peptide designed from the BH3 domain of SPK2 activates autophagy and protects neural cells against OGD injury suggest that this structure may provide the basis for a novel class of therapeutic agents against ischemic stroke.


Assuntos
Isquemia Encefálica/genética , Neurônios/metabolismo , Fragmentos de Peptídeos/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Recombinantes de Fusão/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Sequência de Aminoácidos , Animais , Autofagia/genética , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Isquemia Encefálica/prevenção & controle , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Regulação da Expressão Gênica , Glucose/deficiência , Hipocampo/metabolismo , Hipocampo/patologia , Precondicionamento Isquêmico/métodos , Isoflurano/administração & dosagem , Camundongos , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fragmentos de Peptídeos/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Cultura Primária de Células , Ligação Proteica , Domínios Proteicos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo
16.
Tumour Biol ; 39(3): 1010428317691683, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28347234

RESUMO

MicroRNAs have been reported to be involved in various biological processes. Here, we performed a systematic analysis to explore the clinical value and potential molecular mechanism of miR-145-5p in non-small cell lung cancer. First, a meta-analysis was performed with eligible literature, followed by microRNA microarrays in the Gene Expression Omnibus database, to verify the diagnostic and prognostic values of miR-145-5p. A cohort of 125 clinical paired non-small cell lung cancer samples was next used to detect the level of miR-145-5p and to explore the relationship of miR-145-5p with clinicopathological parameters. The Cancer Genome Atlas database was additionally applied to investigate the role of miR-145-5p in non-small cell lung cancer. The potential targets of miR-145-5p were predicted using 12 online prediction databases to explore the prospective molecular mechanism of miR-145-5p in non-small cell lung cancer. The expression of miR-145-5p in non-small cell lung cancer was significantly lower than that in healthy tissues. And miR-145-5p tended to show better diagnostic performance in lung squamous cell carcinoma than in lung adenocarcinoma. Furthermore, the expression of miR-145-5p was closely associated with lymph node metastasis in non-small cell lung cancer. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes were mainly enriched with enzyme-linked receptor protein signaling pathways, SH3 domain binding, cell leading edge, and adherens junction. The protein-protein interaction network showed that eight hub genes (SMAD4, SMAD2, IRS1, FOXO1, ERBB4, NRAS, ACTB, and ACTG1) might be the key target genes of miR-145-5p in non-small cell lung cancer. The information we obtained might offer new perspectives for clinical diagnosis and treatment for non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Formaldeído , Humanos , Neoplasias Pulmonares/patologia , Inclusão em Parafina , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estudos Retrospectivos , Fixação de Tecidos
17.
Sci Rep ; 7: 43488, 2017 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-28262717

RESUMO

Significant advances have been achieved in the outcomes of patients with myelodysplastic syndromes (MDS) after both HLA-matched sibling donor transplants (MSDT) and non-MSDT, the latter including HLA-matched unrelated donor (MUDT) and haplo-identical donor transplants (HIDT). In this retrospective study, we analyzed the data of 85 consecutive patients with MDS who received allogeneic HSCT between Dec 2007 and Apr 2014 in our center. These patients comprised 38 (44.7%) who received MSDT, 29 (34.1%) MUDT, and 18 (21.2%) HIDT. The median overall survival (OS) was 60.2 months, the probabilities of OS being 63%, 57%, and 48%, at the first, second, and fifth year, respectively. Median OS post-transplant (OSPT) was 57.2 months, the probabilities of OSPT being 58%, 55%, and 48% at the first, second, and fifth year, respectively. The survival of patients receiving non-MSDT was superior to that of MSDT, median OSPT being 84.0 months and 23.6 months, respectively (P = 0.042); the findings for OS were similar (P = 0.028). We also found that using ATG in conditioning regimens significantly improved survival after non-MSDT, with better OS and OSPT (P = 0.016 and P = 0.025). These data suggest that using ATG in conditioning regimens may improve the survival of MDS patients after non-MSDT.


Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/métodos , Agonistas Mieloablativos/uso terapêutico , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Antígenos HLA/genética , Antígenos HLA/imunologia , Haplótipos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/imunologia , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Transplante Homólogo , Doadores não Relacionados
18.
Huan Jing Ke Xue ; 38(9): 3831-3839, 2017 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965266

RESUMO

In order to investigate the effect of biochar on CH4 and N2O emissions from Lou soil, field plot experiments of winter wheat were conducted with five levels of biochar addition (0, 20, 40, 60, and 80 t·hm-2). The fluxes of CH4 and N2O, wheat production, soil organic carbon, soil water content, and temperature of each soil layer were measured. The results showed that the fluxes of CH4 and N2O changed significantly in different growth periods of winter wheat. Compared with the control, the cumulative CH4 uptake under the biochar amendment increased by 12.88%-71.61%. When the biochar addition was ≥ 40 t·hm-2, the cumulative CH4 uptake was significantly higher and the highest uptake was at the level of 40 t·hm-2. Biochar amendment had no significant effect on cumulative N2O emissions and the global warming potential (GDP). The greenhouse gas intensity (GHGI) decreased by 13.24%-22.14%. The wheat yield increased by 1.72%-32.19% after biochar addition. When the applied biochar level was ≥ 40 t·hm-2, the wheat yield increments were significantly higher. The biochar addition of 40 t·hm-2 was the optimal level for increasing the wheat yield. The soil organic carbon and water content under biochar amendment increased by 1.42-2.69 times and 7.08%-11.96%, respectively. The results suggested that Lou soil was the sink of atmospheric CH4 and the emission source of N2O during the winter wheat growth period, and the biochar level of 40 t·hm-2 was the optimal addition amount.


Assuntos
Carvão Vegetal/química , Metano/análise , Óxido Nitroso/análise , Solo/química , Agricultura , Triticum/crescimento & desenvolvimento
19.
Sci Rep ; 6: 27096, 2016 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-27256465

RESUMO

Previous study showed that TIGAR (TP53-induced glycolysis and apoptosis regulator) protected ischemic brain injury via enhancing pentose phosphate pathway (PPP) flux and preserving mitochondria function. This study was aimed to study the role of TIGAR in cerebral preconditioning. The ischemic preconditioning (IPC) and isoflurane preconditioning (ISO) models were established in primary cultured cortical neurons and in mice. Both IPC and ISO increased TIGAR expression in cortical neurons. Preconditioning might upregulate TIGAR through SP1 transcription factor. Lentivirus mediated knockdown of TIGAR significantly abolished the ischemic tolerance induced by IPC and ISO. ISO also increased TIGAR in mouse cortex and hippocampus and alleviated subsequent brain ischemia-reperfusion injury, while the ischemic tolerance induced by ISO was eliminated with TIGAR knockdown in mouse brain. ISO increased the production of NADPH and glutathione (GSH), and scavenged reactive oxygen species (ROS), while TIGAR knockdown decreased GSH and NADPH production and increased the level of ROS. Supplementation of ROS scavenger NAC and PPP product NADPH effectively rescue the neuronal injury caused by TIGAR deficiency. Notably, TIGAR knockdown inhibited ISO-induced anti-apoptotic effects in cortical neurons. These results suggest that TIGAR participates in the cerebral preconditioning through reduction of ROS and subsequent cell apoptosis.


Assuntos
Isquemia Encefálica/genética , Córtex Cerebral/metabolismo , Hipocampo/metabolismo , Precondicionamento Isquêmico , Proteínas/genética , Traumatismo por Reperfusão/genética , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Isquemia Encefálica/prevenção & controle , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Regulação da Expressão Gênica , Glutationa/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Isoflurano/farmacologia , Lentivirus/genética , Lentivirus/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , NADP/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Monoéster Fosfórico Hidrolases , Cultura Primária de Células , Proteínas/antagonistas & inibidores , Proteínas/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo
20.
Oncotarget ; 7(17): 24374-82, 2016 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-27016410

RESUMO

OBJECTIVES: Anoctamin 1 (ANO1) has been found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous study. Herein we showed the clinical relevance of ANO1 alterations with ESCC and esophageal precancerous lesion progression. RESULTS: ANO1 was detected in 38.1% (109/286) and 25.4% (77/303) of tumors in the two cohorts, but in none of morphologically normal operative margin tissues. ANO1 expression was significantly associated with a shorter overall survival (OS), especially in patients with moderately differentiated and stage IIA tumors. In 499 iodine-unstained biopsies from the endoscopic screening cohort in 2005-2007, all the 72 pathologically normal epithelial mucosa presented negative immunostaining, whereas ANO1 expression was observed in 3/11 tumors and 5/231 intraepithelial lesions. 7/8 ANO1-positive cases had developed unfavorable outcomes revealed by endoscopic follow-up in 2012. Analysis of another independent cohort of 148 intraepithelial lesions further confirmed the correlation between ANO1 expression and progression of precancerous lesions. 3/4 intraepithelial lesions with ANO1 expression had developed ESCC within 4-9 years after the initial endoscopic examination. METHODS: Immunohistochemistry (IHC) was performed to examine ANO1 expression in surgical ESCC specimens and two independent cohorts of esophageal biopsies from endoscopic screening in high-incidence area of ESCC in northern China. Association between ANO1 expression, clinico-pathologic parameters, and the impact on overall survival was analyzed. CONCLUSIONS: Positive ANO1 is a promising biomarker to predict the unfavorable outcome for ESCC patients. More importantly, it can predict disease progression of precancerous lesions.


Assuntos
Anoctamina-1/biossíntese , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Proteínas de Neoplasias/biossíntese , Lesões Pré-Cancerosas/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Progressão da Doença , Neoplasias Esofágicas/diagnóstico , Esôfago/metabolismo , Esôfago/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/diagnóstico , Prognóstico
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